JNJ-42226314 (JNJ42226314; JNJ 42226314) is a novel and potent monoacylglycerol lipase (MAGL) inhibitor with a potential to be used for treating neuropathic and inflammatory pain.
Physicochemical Properties
| Molecular Formula | C26H24FN5O2S |
| Molecular Weight | 489.5645 |
| Exact Mass | 489.163 |
| CAS # | 1252765-13-1 |
| PubChem CID | 59625954 |
| Appearance | White to off-white solid powder |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 35 |
| Complexity | 782 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1C([H])=C([H])N=C1C(N1C([H])([H])C([H])([H])N(C([H])([H])C1([H])[H])C1([H])C([H])([H])N(C(C2C([H])=C([H])C3=C(C([H])=C([H])N3C3C([H])=C([H])C(=C([H])C=3[H])F)C=2[H])=O)C1([H])[H])=O |
| InChi Key | IVOACCSOISMVBL-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C26H24FN5O2S/c27-20-2-4-21(5-3-20)32-9-7-18-15-19(1-6-23(18)32)25(33)31-16-22(17-31)29-10-12-30(13-11-29)26(34)24-28-8-14-35-24/h1-9,14-15,22H,10-13,16-17H2 |
| Chemical Name | [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(1,3-thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone |
| Synonyms | JNJ-42226314 JNJ 42226314 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | JNJ-42226314's IC50 values against mouse brain, rat brain, human PBMC, and human HeLa cells are 1.13 nM, 1.88 nM, 0.67 nM, and 0.97 nM, respectively [1]. |
| ln Vivo | In vivo, JNJ-42226314 (ip; 3 mg/kg and 30 mg/kg; 120 minutes) elevates hippocampus 2-AG in a dose-dependent manner [1]. When JNJ-42226314 (ip; 30 mg/kg) was administered, total arousal time increased by up to 8 hours as opposed to just 2 hours [1]. The rat complete Freund's adjuvant (CFA) inflammatory pain model exhibits analgesic effects in response to intraperitoneal injection of JNJ-42226314 (30 mg/kg) [1]. JNJ-42226314's MAGL t1/2 values in rats, mice, and humans are 27.2, 27.6, and 11.4 minutes, respectively [1]. |
| Animal Protocol |
Animal/Disease Models: Male C57Bl/6 mice weighing 20-30g and male SD (SD (Sprague-Dawley)) rats weighing 300-400g [1] Doses: 3mg/kg and 30mg/kg Route of Administration: ip; 120 minutes Experimental Results: Hippocampus in vivo 2-AG increased in a dose-dependent manner. |
| References |
[1]. Pharmacologic characterization of JNJ-42226314, [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a reversible, selective and potent monoacylglycerol lipase inhibitor.J Pharmacol Exp Ther. 20. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~510.66 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (12.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (12.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 6.25 mg/mL (12.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0427 mL | 10.2133 mL | 20.4265 mL | |
| 5 mM | 0.4085 mL | 2.0427 mL | 4.0853 mL | |
| 10 mM | 0.2043 mL | 1.0213 mL | 2.0427 mL |